ANALYTICAL BIOCHEMISTRY
·
2024
·
IF 2.6
Shimeng Duan,Haiou Chen,Anyun Xu,Ying He,Meng Li,Ru Zhang,Ruilin Zhang,Huiping Bai
In this study, a simple electrochemical sensor based on l -arginine membrane (P-L-arg/GCE) was developed for rapid and sensitive detection of MDMA and MDA. A polyarginine membrane was obtained through one-step direct electropolymerization, which provides more reaction sites for the analyte and improves the sensitivity of the sensor. Following the optimized selection parameters, the MDMA detection range was established at 1.0 × 10 −7 ∼3.5 × 10 −5 mol L −1 , with a detection limit of 3.3 × 10 −8 mol L −1 . Similarly, the detection range for MDA was established at 1.0 × 10 −7 ∼5.3 × 10 −5 mol L −1 with a detection limit of 3.3 × 10 −8 mol L −1 . Additionally, the potential oxidation mechanism of MDMA and MDA during the REDOX process was analyzed by cyclic voltammetry . Furthermore, the proposed sensor exhibited superior selectivity, excellent reproducibility, and satisfactory stability. The proposed sensors can be used for reliable monitoring of MDMA or MDA in human urine and hair samples, respectively, and it has acceptable analytical reliability and enormous potential for practical applications.
研究领域:
分析化学
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毒理学
·
材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2024
·
IF 2.7
Boyang Xu,Jun Yan,Yangtao Zhou,Feng Zhang,Binjie Wang,Jiye Wang,Yuanzhao Wu,Yu Xu
As global regulations on synthetic cannabinoids tighten, illicit vendors increasingly turn to new structures of synthetic cannabinoids to evade legal scrutiny. MDA-19, a novel synthetic cannabinoid, exhibited significant agonistic effects on type 2 cannabinoid receptors in vivo and showed emerging trends of abuse in illicit markets. However, research on the toxicological effects of MDA-19 remains scarce. In this study, we examined the effects of MDA-19 on neurodevelopment, behavior, oxidative stress, and metabolomics by exposing zebrafish embryos to MDA-19 solutions with concentrations of 1, 10, and 20 mg/L over 5 days. Results revealed that exposure to 10 and 20 mg/L of MDA-19 accelerated hatching in zebrafish embryos but led to reduced body length without affecting mortality or malformation. Furthermore, exposure to all concentrations of MDA-19 resulted in diminished swimming ability and reduced activity time in zebrafish. Transgenic zebrafish ( hb9 -GFP) exposed to MDA-19 exhibited impaired development of spinal motor neurons. Notably, exposure to 20 mg/L MDA-19 increased the levels of reactive oxygen species (ROS) in zebrafish and elevated the activity of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT), while the levels of the lipid oxidation product malondialdehyde (MDA) remained unaffected. Nontargeted metabolomics analyses showed that MDA-19 interfered with multiple metabolic pathways affecting energy metabolism, such as alanine, aspartate, and glutamate metabolism; the citric acid cycle (TCA cycle), pantothenate, and coenzyme A biosynthesis; and purine metabolism. In conclusion, the present study provided the essential evidence for the neurotoxic effects of MDA-19, which was associated with impaired neurodevelopment, dysregulation of oxidative stress homeostasis, and altered energy metabolism.
研究领域:
毒理学
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神经生物学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2017
·Vol. 14
·期 5
·5307-5312
·
IF 1.39
Binggao Wang,Zhibo Xing,Fengmei Wang,Xinyan Yuan,Yanhui Zhang
In order to improve outcomes after breast cancer treatment, it is essential to understand the mechanisms of action of potential therapeutic agents. The effect of fangchinoline (FAN) on migration and apoptosis of human breast cancer MDA-MB-231 cells and its underlying mechanisms were investigated. MDA-MB-231 cells were treated with different concentrations of FAN, growth inhibition rates were measured by MTT assay and morphological changes of apoptotic cells were observed by Hoechst staining. The wound-healing assay was used to determine of the effect of FAN on the migration of MDA-MB-231 cells. ELISA was used to detect the expression of MMP-2 and -9 in MDA-MB-231 cells treated with different concentrations of FAN and western blot analysis was used to quantify expression of NF-κβ and Iκβ proteins in the same cells. Our results showed that FAN significantly inhibited the growth of MDA-MB-231 cells in concentration-dependent manner and it induced MDA-MB‑231 cell apoptosis. With the high FAN concentrations and long exposure times, the levels of MMP-2 and -9 decreased and the expression of NF-κβ decreased, while the expression of Iκβ protein increased. Based on these results, the antitumor effects of FAN on breast cancer cells can be explained at least partially by inducing apoptosis and inhibiting the migration of MDA-MB-231 cells.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2021
·Vol. 22
·期 21
·11466
·
IF 5.924
Miaomiao Qi,Xiang Liu,Ying Zhou,Haoyu Wang,Ying Zhao,Jing Ren,Jin Xiang
G protein-coupled estrogen receptor 1 (GPER1) is a potential therapeutic target for treating triple-negative breast cancers (TNBC). However, modulators for GPER1 that can be used to treat TNBC have not appeared. Berberine (BBR) is a bioactive isoquinoline alkaloid with high oral safety. In recent years, BBR has shown an inhibitory effect on TNBC tumors such as MDA-MB-231, but the molecular target remains unclear, which hinders related clinical research. Our work proved that BBR is a modulator of GPER1 that can inhibit cell viability, migration, and autophagy of MDA-MB-231 cells. The inhibitory effect of BBR on MDA-MB-231 cells has a dependence on estrogen levels. Although BBR promoted the proteasome, which is a major factor in the degradation of GPER1, it could still induce the protein level of GPER1. Correspondingly, the transcription of cellular communication network factor 2 (CCN2) was promoted. BBR could bind to GPER1 directly and change the secondary structure of GPER1, as in the case of 17β-estradiol (E2). In addition, BBR induced not only a high degree of co-localization of GPER1 and microtubule-associated protein 1 light chain 3 (MAP1LC3), but also the accumulation of sequestosome 1 (SQSTM1/p62) by the inhibition of the nuclear translocation of the nuclear factor-kappa B (NF-κB) subunit (RELA/p65), which indicates NF-κB inhibition and anti-cancer effects. This result proved that the promotional effect of BBR on the GPER1/NF-κB pathway was closely related to its inhibitory effect on autophagy, which may serve as a new mechanism by which to explain the inhibitory effect of BBR on MDA-MB-231 cells and expand our understanding of the function of both BBR and GPER1.Keywords:berberine;binding;co-localization;GPER1;MAP1LC3;NF-κB
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Lingli Zhang,Chengguang Wu,Shansong Mu,Wei Xue,Dong Ma
To enhance the chemotherapy effect to MDA-MB-231, a glutathione (GSH)-sensitive amphiphilic hyperbranched poly (amide-amine) (mPEG-PLGA-HPAA) was synthesized, and the anti-cancer drug, paclitaxel (PTX) was then encapsulated into the mPEG-PLGA-HPAA micelles. The mPEG-PLGA-HPAA containing a large number of disulfide bonds could degrade and then consume the GSH intracellularly, which was expected to enhances the sensitivity of MDA-MB-231 cells to PTX. It was found that the mPEG-PLGA-HPAA/PTX nanoparticles could respond to the GSH and showed a GSH-controlled PTX release. Simultaneously, the mPEG-PLGA-HPAA/PTX nanoparticles significantly enhanced the efficacy of PTX by inhibiting MDA-MB-231 cells proliferation and inducing cells apoptosis, performing the self-sensitization effect of chemotherapy. Moreover, the drug carrier of mPEG-PLGA-HPAA exhibited excellent biocompatibility in vitro and in vivo . These results indicated that the self-sensitized drug carrier is a promising route to maximize the therapeutic effect and minimize the side effects of chemotherapy drugs used currently in clinical.
研究领域:
药学
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肿瘤学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Wen-Juan Tang,Di Xu,Ming-Xing Liang,Guan-Qun Wo,Wen-Quan Chen,Jin-Hai Tang,Wei Zhang
Triple-negative breast cancer (TNBC) is more prone to recurrence and metastasis relative to other subtypes of breast cancer, leading to an extremely poor prognosis. The increasing potential chemoresistance of TNBC patients is mainly due to that tumor cells escape from apoptosis. In recent years, statins have demonstrated extensive anti-tumor effects. It is worth noting that statins have more effective anti-tumor effects on TNBC cells and drug-resistant breast cancer cells. Therefore, this study examines the superior cytotoxic effects of statins on TNBC cell lines and further explores their potential therapeutic mechanisms. We detected different cell phenotypes and found that statins significantly reduced the cell viability of TNBC cells. Specifically, pitavastatin showed an obvious induction in cell death, cell cycle arrest and oxidative stress in TNBC MDA-MB-231 cells. The reversal effect of iron chelator desferrioxamine (DFO) on the morphological and molecular biological changes induced by pitavastatin has revealed a new mode of cell death induced by pitavastatin: ferroptosis. This ferroptotic effect was strengthened by the decreased expression of glutathione peroxidase 4 (GPx4) as well as newly discovered ferroptosis suppressor protein 1 (FSP1). The data showed that ferroptotic death of MDA-MB-231 cells is autophagy-dependent and mediated by the mevalonate pathway. Finally, we found that therapeutic oral doses of statins can inhibit the growth of transplanted tumors, which establishes statins as a potential treatment for TNBC patients. In conclusion, we found pitavastatin could induce autophagy-dependent ferroptosis in TNBC cells via the mevalonate pathway which may become a potential adjuvant treatment option for TNBC patients.
研究领域:
肿瘤学
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药理学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 7
·969-978
·
IF 2.571
Ding Ting,Yang Luo-Jie,Zhang Wei-Dong,Shen Yun-Heng
ObjectivesTo screen the cytotoxic activity of six secondary metabolites isolated from soil fungus Aspergillus niger. Importantly, to investigate the mechanism that pyoluteorin induced human triple-negative breast cancer MDA-MB-231 cells apoptosis in vitro.MethodsThe cell viability assay was tested with CTG assay. Cell cycle, apoptosis and intracellular reactive oxygen species (ROS) production assay were tested with flow cytometry. Additionally, intracellular ROS production assay and mitochondrial membrane potential assay were determined with laser scanning confocal microscopy. The expression of apoptosis-related proteins was determined with Western blot.Key findingsPyoluteorin displayed significantly selective cytotoxicity against human triple-negative breast cancer MDA-MB-231 cells (IC50 = 0.97 µm) with low toxicity against human breast epithelial cell MCF-10A. It was found that pyoluteorin could arrest MDA-MB-231 cells cycle at G2/M phase and induce cell apoptosis. Further experiments demonstrated that the apoptosis-inducing effect of pyoluteorin was related to reduction of mitochondrial membrane potential, accumulation of ROS and change of apoptosis-related protein expressions.ConclusionOur studies revealed that pyoluteorin had potent proliferation inhibition against MDA-MB-231 cells through arresting cell cycle at G2/M phase and inducing caspase-3-dependent apoptosis by mitochondrial pathway, implying that pyoluteorin may be a potential lead compound for drug discovery of human triple-negative breast cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2023
·Vol. 20
·期 4
·e202200523
·
IF 2.9
Zhonghua An,Xuelin Feng,Mengjia Sun,Yifan Wang,Hongbo Wang,Yanling Gong
Chamomile essential oil (CEO) is extracted from chamomile and mainly used in aromatherapy. The chemical constituents and its antitumor activity on Triple-negative breast cancer (TNBC) was explored in the present study. Gas chromatography-mass spectrometry (GC/MS) was employed to analyze the chemical constituents of CEO. The cell viability, migration and invasion of TNBC cell MDA-MB-231 were measured using MTT, wound scratch and Transwell assay, respectively. The protein expression of PI3K/Akt/mTOR signaling pathway was determined by Western blot. CEO is rich in terpenoids (63.51 %), among which the identified terpenoids and their derivatives are mainly Caryophyllene (29.57 %), d-Cadinene (12.81 %), Caryophyllene oxide (14.51 %), etc. Three concentration of CEO (1, 1.5, 2 μg/mL) significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells with a dose dependent manner. Moreover, the phosphorylation of PI3K, Akt and mTOR was inhibited by CEO. The results revealed that there was abundant terpenoids in the CEO which account for 63.51 %. CEO significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells, exhibiting antitumor effect on TNBC. The antitumor effect of CEO might attribute to its inhibition on PI3K/Akt/mTOR signaling pathway. However, further study should be conducted in more TNBC cell lines and animal models to provide further evidence for TNBC treatment by CEO.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Xin Liu,Dawei Fan,Chenchen Zhang,Xinrong Shao,Hongmin Ma,Yong Zhang,Xueying Wang,Qin Wei,Huangxian Ju
An ultrasensitive photoelectrochemical (PEC) antifouling immunosensor was proposed using BiOBr/FeTPPCl/BiOI as matrix and polyacrylic acid (PAA)/polyethylene glycol (PEG) as hybrid antifouling interface for MDA-MB-231 detection. An indium tin oxide (ITO) electrode was successively modified with bismuth oxybromide (BiOBr) with layered crystal structure, which was sensitized with tetraphenyl iron(Ⅲ) porphyrin chloride (FeTPPCl) to widen the absorption range of visible light, and decorated with bismuth oxyiodide (BiOI) nanosheets to improve the PEC response. The joint action of PAA and PEG could offset the adsorption of non-specific proteins on the immunosensing interface for obtaining good antifouling performance. Based on the specific interaction of sialic acid (SA) on the cytomembrane with 3-aminophenylboronic acid (APBA), and the synergistic antifouling effect of PEG and PAA, a simple PEC immunosensing method was developed for the quantitative determination of MDA-MB-231 cells. This proposed antifouling PEC immunosensor exhibited a wide linear range (1 × 10 2 ∼ 1 × 10 6 cells·mL -1 ) and a low detection limit (30 cells·mL -1 ). The development of antibody-free immunosensors may improve the application for the diagnosis of human breast cancer.
研究领域:
材料科学
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分析化学
·
生物化学
·
癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
Cancer Medicine
·
2020
·Vol. 9
·期 7
·2564-2578
·
IF 3.491
Yubo Guo,Yingyi Fan,Xiaohua Pei
Triple-negative breast cancer (TNBC) is a basal-like cancer which is considered to be more intrusive, have a poorer prognosis and chemoresistance. TNBC is characterized by the presence of epithelial to mesenchymal transition (EMT) that plays a major role in the progression of the cancer. In the present study, we first use a classic prescription of Chinese medicine Fangjihuangqi Decoction to treat TGFβ1-induced MDA-MB-231 cells in vitro. Our data showed that TGFβ1-induced MDA-MB-231 cell morphology change, promoted MDA-MB 231 invasion, increased Vimentin expression, and decreased E-cadherin expression. Further, Fangjihuangqi Decoction-medicated serum (FHS) treated both MDA-MB 231 cells and TGFβ1-induced MDA-MB-231 cells. Results showed that Fangjihuangqi Decoction could inhibit cell proliferation, reduce cell invasion, increase E-cadherin expression, and decrease EMT markers. Secondly, we established a xenograft tumor zebrafish model to assess Fangjihuangqi Decoction inhibition of cancer cell proliferation and invasion. Our results indicated that Fangjihuangqi Decoction could inhibit tumor growth, restrain the sprouts number of tumor neovascularization, and reduce the length of tumor neoplastic lymphatics by increasing E-cadherin expression and decreasing EMT markers in TNBC xenograft tumor zebrafish model. Overall, our studies provide evidences that Fangjihuangqi Decoction could inhibit TNBC, reverse EMT, and contribute to antimetastasis by increasing E-cadherin expression and decreasing EMT markers, which provide an experimental basis for clinical application of Fangjihuangqi Decoction on TNBC treatment.
研究领域:
肿瘤学
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
Foods
·
2022
·Vol. 11
·期 9
·1176
·
IF 5.561
Wenjie Wang,Zhiwen Zhang,Xiaoying Liu,Xiaoji Cao,Lianzhu Wang,Yuting Ding,Xuxia Zhou
Malondialdehyde (MDA) is one of the representative end products under lipid peroxidation, indicating the degree of lipid oxidation in foods. However, compounds in pickled products, especially the nitrite in salted lean pork can react with MDA under the acidic condition, leads to the loss of MDA and an underestimation on lipid oxidation through the conventional assay. In this study, the quantification for MDA in the sample containing sodium nitrite were found lacking accuracy by the thiobarbituric acid (TBA) assay and chromatography assay based on alkaline hydrolysis as the reaction between them were difficult to be completely inhibited. Among other trials, the improvement GC-MS analysis utilizing deuterium substituted MDA (MDA-d2) as an internal standard and applying perfluorophenylhydrazine (PFPH) as a derivative reagent can reduce the deviations from the presence of nitrite in the salted lean pork meat and the recovery is between 93.9% and 98.4% and coefficient of variation for the intermediate precision is between 1.1 and 3.5% using the method. The advanced gas chromatograph mass spectrometer (GC-MS) assay also has a very low detection limit (0.25 ng/mL) with both hydrolysis types.Keywords:malondialdehyde;lipid peroxidation;pickled products;nitrite;GC-MS
研究领域:
食品科学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Wei Wu,Jiaen Huang,Yuling Li,Jiaxi Chen,Xiaowei Kuang,Manzhen Ye,Rui Chen,Junli An,Zunnan Huang,Jing Sun
Cancer immunotherapy has revolutionized oncology by leveraging host immunity to eliminate malignant cells. In this study, five iridium(III) complexes (Ir1–Ir5) were synthesized and evaluated for their in vitro antitumor activity against various tumor cell lines. Among these, Ir4 and Ir5 exhibited the highest cytotoxicity and the most rapid cellular uptake in MDA-MB-231 cells. Colocalization experiments confirmed their accumulation in the endoplasmic reticulum (ER) and their ability to induce pyroptosis. Additionally, both complexes triggered ER stress, leading to increased calreticulin exposure on the cell surface, high-mobility group box 1 secretion, and ATP release, which collectively promoted immunogenic cell death. In vivo, a triple-dose Ir4 vaccine regimen significantly suppressed tumor growth compared to other treatment groups. These findings highlight the potential of Ir4-based novel triple-dose vaccination as a promising cancer immunotherapy strategy.
研究领域:
肿瘤学
·
免疫学
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子